Resumen

The purpose of this study was to evaluate the articular cartilage-regenerating capacity of RHH646 in the knee as well as to assess safety and tolerability in participants with knee osteoarthritis.

Descripción detallada

This was a non-confirmatory, randomized, Investigator and participant blinded, two-arm, placebo controlled, Phase IIa study to assess safety, tolerability, and efficacy of orally administered RHH646 in adult participants with symptomatic, mild to moderate radiographic knee osteoarthritis in the target knee and with pain requiring analgesic therapy. The study comprised of a Screening period (up to 6 weeks), a treatment period (52 weeks) and a follow up period (4 weeks after the last administration of study treatment) before the End of Study (EOS) visit. The total duration for each participant was up to 62 weeks.

Elegibilidad

Edad mínima: 35 YearsEdad máxima: 75 YearsSexo: ALL

Criterios de inclusión

Participant is ≥35 and ≤75 years old, at time of screening
Participants must weigh at least 50 kg to participate in the study and must have a body mass index (BMI) ≤35 kg/m2. BMI = Body weight (kg) / \[Height (m)\]2
Diagnosis of tibiofemoral OA in at least one knee by standard American College of Rheumatology clinical and radiographic criteria (Altman et al 1986) at screening
K\&L grade 2 to 3 OA in the target knee evaluated with X-Ray by the Central Reader at screening
Predominantly medial tibiofemoral compartment involvement defined as medial Joint Space Narrowing (medJSN) 1-2 (Altman et al 1995; Altman, Gold 2007) and medJSN \> lateral Joint Space Narrowing (latJSN) in the target knee evaluated with X-Ray by the Central Reader at screening
Symptomatic disease, defined as having pain in the target knee at least 3 days per week during the last 3 months from screening that is relieved by analgesic therapy (e.g. acetaminophen or non-steroidal anti-inflammatory drugs), according to the investigator's evaluation and judgment of the patient's history

Criterios de exclusión

Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception. In EEA countries, women of child-bearing potential will be excluded from participation in this trial, irrespective of the use of highly effective methods of contraception.
Arthroscopy of the target knee within the 6 months prior to screening or planned arthroscopy during the study
Previous surgical treatment of the target knee using mosaicplasty, microfracture, meniscectomy \>50% or osteotomy; planned surgery for either knee during the study
Unstable target knee joint (including, but not limited to, post-traumatic or congenital laxity) or insufficiently reconstructed ligaments based on medical history and/or physical examination by the investigator
Participant has severe malalignment (valgus or varus deformity) in the target knee \>7.5° based on X-ray evaluation by the Central Reader at screening.
K\&L grade 4 OA in either knee
Presence of severe hip OA that either (i) alters lower limb function to a degree that increases or abnormally changes the mechanical forces in the knee while walking, according to investigator's evaluation or (ii) currently requires or is likely to require specific medical or surgical management during the study period
Other pathologies affecting the knee, including subchondral insufficiency fractures, bone fracture (acute or subacute within the 6 months prior to screening) or bone bruise, osteonecrosis, malignant bone marrow infiltration, solid tumors, and/or patellofemoral dysplasia based on clinical assessment, or imaging
Known autoimmune disease with inflammatory arthritis (including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus), crystal-induced arthritides (gout or pseudogout arthritis), active acute or chronic infection of the knee joint, Lyme disease involving the knee, reactive arthritis, systemic cartilage disorders, moderate to severe fibromyalgia, a known systemic connective tissue disease or a widespread pain index \>4.
Inability to undergo MRI (e.g., claustrophobia, body size, leg not fitting in the coil) or contraindications to MRI (e.g., non MRI-compatible metallic implants, metallic foreign bodies, pacemaker, defibrillator)

A Randomized, Placebo Controlled, Investigator and Participant-blinded Study Investigating Safety, Tolerability, and Efficacy of RHH646 in Participants With Knee Osteoarthritis

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

RHH646

Placebo

Ubicaciones

Novartis Investigative Site

Novartis Investigative Site

Patrocinadores